Obesity is now recognized as a chronic disease that requires treatment to reduce its associated health risks. The increase in obesity is of concern because of the health risks associated with obesity, including coronary heart disease, strokes, hypertension, type 2 diabetes mellitus, dyslipidemia, sleep apnea, osteoarthritis, gall bladder disease, depression, and certain forms of cancer (e.g., endometrial, breast, prostate, and colon). The negative health consequences of obesity make it the second leading cause of preventable death in the United States. See, McGinnis M, Foege W H., “Actual Causes of Death in the United States,” JAMA, 270, 2207 12 (1993).
It is believed that 5-10% reduction of body weight can substantially improve metabolic values, such as blood glucose, blood pressure, and lipid concentrations.
Currently available prescription drugs for managing obesity generally reduce weight by inducing satiety or decreasing dietary fat absorption. Satiety is achieved by increasing synaptic levels of norepinephrine, serotonin, or both. For example, stimulation of serotonin receptor subtypes 1B, 1D, and 2C and 1- and 2-adrenergic receptors decreases food intake by regulating satiety. See, Bray G A, “The New Era of Drug Treatment. Pharmacologic Treatment of Obesity: Symposium Overview,” Obes. Res., 3(suppl 4), (1995). Adrenergic agents (e.g., diethylpropion, benzphetamine, phendimetrazine, mazindol, and phentermine) act by modulating central norepinephrine and dopamine receptors through the promotion of catecholamine release. Older adrenergic weight-loss drugs (e.g., amphetamine, methamphetamine, and phenmetrazine), which strongly engage in dopamine pathways, are no longer recommended because of the risk of their abuse. Fenfluramine and dexfenfluramine, both serotonergic agents used to regulate appetite, are no longer available for use.
Because of the side effects expressed and the development of addiction resulting from the use of these psychoactive substances, an effective and safe medicine of central effect is still not available. Thus, there still exists a need for a more effective and safe therapeutic treatment for reducing or preventing obesity and related metabolic disorders.
In addition to obesity, there also exists an unmet need for treatment of substance addiction.
Tobacco addiction represents the most important preventable cause of illness and death in our society, responsible for thousands of deaths each year. Half of all smokers will die of diseases directly related to tobacco use, and many smokers will suffer significant morbidity. Approximately 15 million smokers try to quit, but only one million of those succeed in smoking cessation each year.
Cigarette smoke contains a large number of very complex substances the most important of which is nicotine, this being the substance to which cigarette smokers develop an addiction. Several pharmacotherapies have proven effective for the treatment of tobacco addiction. These include nicotine replacement therapies in the form of gum, patch, nasal spray and inhaler. Non-nicotine pharmacologic therapies have been developed as a method of treating nicotine addiction. Possible reagents include nicotine blockade therapy, drugs affecting serotonergic neurotransmission, anti-depressants, anxiolytics, clonidine and airway sensory replacement (Rose, 1996; and Cinciripini et al., 1998 Oncology 12: 249-256). Nicotine blockade therapy (also referred to as nicotine receptor antagonists) utilizes compounds that occupy nicotine receptors, thereby attenuating the reward received from tobacco usage (Clarke, 1991 Br. J. Addict. 86: 501-505). However, there is a need for more effective treatment for tobacco addiction.
The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. Cannabinoid receptors are activated by three major groups of ligands, (a) endocannabinoids (produced by the mammalian body), (b) plant cannabinoids (such as THC, produced by the cannabis plant) and (c) synthetic cannabinoids (such as HU-210, first synthesized in 1988 from (1R,5S)-Myrtenol). These cannabinoids exert their effects by binding to cannabinoid receptors located in the cell membrane. Endocannabinoids have been implicated in a wide variety of physiological and pathophysiological processes. To date, most drugs used to interact with the endocannabinoid system are derived from cannabis. Cannabis has received the most popularity as a raw material for products such as marijuana and hashish and its regular use can result in the development of dependence.
Two cannabinoid receptors have been characterized: cannabinoid receptor 1 (CB1), a central receptor found in the mammalian brain and peripheral tissues and cannabinoid receptor 2 (CB2), a peripheral receptor found only in the peripheral tissues. The CB1 receptor is mainly expressed in several brain areas including the limbic system (amygdala, hippocampus), hypothalamus, cerebral cortex, cerebellum, and basal ganglia. Compounds that are agonists or antagonists for one or both of these receptors have been shown to provide a variety of pharmacological effects. See, for example, Pertwee, R. G., Pharmacology of cannabinoid CB1 and CB2 receptors, Pharmacol. Ther., (1997) 74:129-180 and Di Marzo, V., Melck, D., Bisogno, T., DePetrocellis, L., Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action, Trends Neurosci. (1998) 21:521-528.
The therapeutic effect of an extremely diluted (or ultra-low) form of antibodies potentized by homeopathic technology (activated potentiated form) has been discovered by the inventor of the present patent application, Dr. Oleg I. Epshtein. U.S. Pat. No. 7,582,294 discloses a medicament for treating Benign Prostatic Hyperplasia or prostatitis by administration of a homeopathically activated form of antibodies to prostate specific antigen (PSA).
The S-100 protein is an acidic cytoplasmic protein expressed in the nervous system. It has been suggested that the S-100 protein has a role in anxiety. See Ackermann et al., S100A1-deficient male mice exhibit increased exploratory activity and reduced anxiety-related response, Biochim. Biophys. Acta. 2006, 63(11):1307-19; Diehl et al., Long lasting sex-specific effects upon behavior and S100b levels after maternal separation and exposure to a model of post-traumatic stress disorder in rats, Brain Res., 2007, 144:107-16, all of which are incorporated herein by reference.
Ultra-low doses of antibodies to S-100 protein have been shown to have anxiolytic, anti-asthenic, anti-aggressive, stress-protective, anti-hypoxic, anti-ischemic, neuroprotective and nootropic activity. See Castagne V. et al., Antibodies to S100 proteins have anxiolytic-like activity at ultra-low doses in the adult rat, J. Pharm. Pharmacol. 2008, 60(3):309-16; Epshtein O. I., Antibodies to calcium-binding S100B protein block the conditioning of long-term sensitization in the terrestrial snail, Pharmacol. Biochem. Behav., 2009, 94(1):37-42; Voronina T. A. et al., Chapter 8. Antibodies to S-100 protein in anxiety-depressive disorders in experimental and clinical conditions. In “Animal models in biological psychiatry”, Ed. Kalueff A. V. N-Y, “Nova Science Publishers, Inc.”, 2006, pp. 137-152, all of which are incorporated herein by reference.
There is a continuing need for new drug products with desired therapeutic efficacy for treatment of excess body mass or obesity and substance addiction.